Is CHRND p.Val511Met (c.1531G>A) pathogenic?

CHRND p.Val511Met (c.1531G>A) is classified Uncertain significance in CHRND (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-26). AlphaMissense: likely benign (0.1114); Ultra-rare (popmax 0.016%, afr); Associated with lethal multiple pterygium syndrome.

What condition is associated with CHRND p.Val511Met (c.1531G>A)?

CHRND p.Val511Met (c.1531G>A) is associated with lethal multiple pterygium syndrome (ClinVar).

How common is CHRND p.Val511Met (c.1531G>A) in the general population?

CHRND p.Val511Met (c.1531G>A) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about CHRND p.Val511Met (c.1531G>A)?

AlphaMissense predicts likely benign (score 0.1114) — an in-silico prediction, not a clinical call.

CHRND p.Val511Met

c.1531G>A · rs759384601 · VCV1360672

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1114 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lethal multiple pterygium syndrome

Computational evidence

Protein change
AlphaMissense	0.1114	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.43, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 9,093 bp · p 0.12 · regional, not allelic
Overall
CADD	17.58	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,924 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00155% 25/1,613,750 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,244
Admixed American	0.005%	20,002
Remaining individualsnot grpmax-eligible	0.0032%	31,240
South Asian	0.0011%	91,088
European (non-Finnish)	0.000593%	168,578

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHRND
Protein: p.Val511Met
Coding: c.1531G>A
MANE Select: NM_000751
dbSNP: rs759384601
Type: single nucleotide variant
Location: chr2:232535289 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21 · 25 PDB
Residue 511: a β-strand

Full CHRND gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

lethal multiple pterygium syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHRND c.1252+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHRND c.821-2A>C Pathogenic/Likely pathogenic ★★ same condition
CHRND c.933-2A>G Likely pathogenic ★★ same condition
CHRND p.Arg336Gln Likely pathogenic ★★ same condition
CHRND p.Arg43Trp Pathogenic/Likely pathogenic ★★ same condition
CHRND p.Cys257Arg Pathogenic/Likely pathogenic ★★ same condition
CHRND p.Trp78Ter Pathogenic ★★ same condition
CHRND p.Trp83Ter Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/chrnd-p-val511met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown